This application is requesting support for the purchase of a confocal/multiphoton microscope to replace a heavily used, older generation confocal microscope. The instrumentation is needed by a group of investigators with common interests in environmental health. Major uses of this instrumentation will include: studies of tissue, cellular and subcellular distribution and molecular mechanisms of cellular injury caused by a group of inherently fluorescent environmental toxicants; mechanisms by which estrogen receptor a (ERa) interactions with Spl protein participate in growth and gene expression in breast cancer cells; inhibitory aryl hydrocarbon receptor (AhrR)-ERa crosstalk; mechanisms of inhibition of colon and pancreatic cancer by PPARgamma agonists; chemopreventive effects of n-3 polyunsaturated fatty acids and the involvement of reactive oxygen species and mitochondria in colon cancer; the role of Nkx transcription factors to control developmental processes; and the role of environmental insults on developmental toxicity and neurodevelopment. The requested system will greatly facilitate our ability to perform repeated measurements over time with higher throughput and with less cellular and tissue damage. Unique capabilities of this imaging system that will allow us to perform these studies include: 1) limited biological damage to living cells and tissues; 2) in focus, optical sections of thick samples; 3) ability to view deep into slices and tissues; 4) the ability to image a variety of fluorescent molecules; 5) increased ability to obtain three-dimensional data sets from cells and tissues and do this over time; 6) considerable time savings through multi-time series experiments; and 7) the diversity of experiments that can be performed on the hardware/software combination. This new technology will provide faculty, postdoctoral fellows and students with access to a state-of-the-art imaging facility and will facilitate the ongoing research of the major and minor users. [unreadable] [unreadable] [unreadable]